Drugs are now determined in serum-hundreds of thousands of samples per year in the United States alone--by high pressure liquid chromatography (HPLC). Protein must first be removed from the serum. Otherwise the HPLC columns are quickly ruined. Internal- surface reversed-phase (ISRP) HPLC columns afford such determinations without requiring the prior removal of protein from the serum. With Phase I assistance, Regis synthesized the first commercial ISRP, glycinephenylalanine-phenylalanine (GFF); put it's synthesis on a production basis; characterized GFF; brought reproducible, efficient, long-lived, and selective GFF ISRP high-efficiency HPLC columns to market (over 600 sold to date); demonstrated several real-life ISRP GFF applications; and publicized the effort in a variety of ways. With Phase II assistance, Regis will develop further demonstrative applications of GFF; and restudy the synthesis so as to produce better successors. Complimentary ISRP's will then be synthesized, characterized, introduced, and supported. Through a program with Dr. Regnier at Purdue a wide variety of conceptually new ISRP materials will be synthesized. Non-enzymatic syntheses will lower costs radically; and the ISRP concept will be expanded to address the broad field of separating small molecules from large ones.